The long-range goal of this project is to determine the immunological defect(s) causing increased susceptibility of chronic alcoholics to pneumococcal pneumonia. Chronic ethanol intake predisposes humans and laboratory animals to infection, particularly of the respiratory tract. Streptococcus pneumoniae is the leading cause of pneumonia in alcoholics, who experience increased severity of disease, a higher incidence of bacteremia, and elevated mortality rates. A model of pneumococcal pneumonia has been developed using a well characterized regimen of chronic ethanol feeding in rats. After 7 days of ethanol administration, the rats exhibit increased susceptibility to an experimental transtracheal pneumococcal infection. There is uncontrolled growth of bacteria in their lungs despite adequate pulmonary recruitment of polymorphonuclear leukocytes (PMNL). This indicates a functional defect in pulmonary bactericidal activity in chronically intoxicated rats. This proposal is designed to examine both extracellular and cellular pulmonary defenses against pneumococci. Extracellular killing of bacteria by free fatty acids in lung surfactant will be examined in Specific Aim 1. In Specific Aim 2, bacteriostasis by iron-binding proteins in alveolar fluid will be quantitated and alterations in transferrin structure examined. PMNL functions will be studied in Specific Aims 3 and 4. Attachment and engulfment of pneumococci will be measured by flow cytometry. Intracellular killing of the organisms will be quantitated by a viable plate count method. PMNL opsonin receptor function, membrane fluidity, oxidative respiration, and degranulation will be determined to elucidate the mechanism(s) responsible for PMNL dysfunction in the ethanol-fed host. In Specific Aim 5 the time course for recovery of pulmonary defenses after discontinuation of ethanol feeding will be examined, and attempts will be made to restore pulmonary defenses in ethanol-fed rats by lipid supplementation and cytokine treatment. These studies will focus on factors that predispose alcoholics to pneumonia, but also will provide valuable information about the mechanisms responsible for generalized impairment of antimicrobial host defense in the chronic alcoholic.